Water → HCID 59201599, compound
Reaction equation
[NH2:1][CH2:2][CH2:3][O:4][C@:5]([C@@H:16]1[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1)([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=1)[CH2:6][CH2:7][CH3:8].CCN(CC)CC.Cl[C:37]([O:39][CH3:40])=[O:38].O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:15][C:11]1[CH:10]=[C:9]([C@@:5]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:17]2)([O:4][CH2:3][CH2:2][NH:1][C:37]([O:39][CH3:40])=[O:38])[CH2:6][CH2:7][CH3:8])[CH:14]=[CH:13][CH:12]=1Participants
Conditions
- Temperature
- 2.5 °C
Procedure
To a solution of (R)-tert-butyl 3-((R)-1-(2-aminoethoxy)-1-(3-chlorophenyl)butyl)piperidine-1-carboxylate (410 mg, 1 mmol) and DMAP (61 mg, 0.5 mmol) in dry CH2Cl2 (3 mL), Et3N (303 mg, 3 mmol) was added. The resulting mixture was cooled to 0-5° C. using a ice-water bath, a solution of methyl chloroformate (472 mg, 5 mmol) in dry CH2Cl2 (2 mL) was added dropwise. After addition, the reaction mixture was stirred for 1-2 h at 0-5° C. Upon completion of the reaction water (5 mL) was added and the aqueous layer was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with 10% citric acid (2×10 mL) and brine, then dried over Na2SO4, filtered and concentrated to afford (R)-tert-butyl 3-((R)-1-(3-chlorophenyl)-1-(2-(methoxycarbonylamino)ethoxy)butyl)piperidine-1-carboxylate (460 mg, 98%), which was used in the next step without further purification.
Workup
- additionAfter addition
- additionwas added
- extractionthe aqueous layer was extracted with CH2Cl2 (3×15 mL)
- washThe combined organic layers were washed with 10% citric acid (2×10 mL) and brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-a955ddf2992541d98b49ea2cfd05dd90
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08487108B2
Reaction notes
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